Mi Yanjun, Li Yongwen, He Zhuo, Chen Donghan, Hong Qingqi, You Jun
Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, Fujian Province, 361003, People's Republic of China.
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, Fujian Province, 361003, People's Republic of China.
Cancer Manag Res. 2021 Feb 2;13:899-912. doi: 10.2147/CMAR.S287775. eCollection 2021.
Linc-ROR is a long non-coding RNA, that is found aberrantly expressed in various human cancers. We aim here to unveil the role of Linc-ROR in gastric cancer (GC) progression.
qPCR was used to determine gene expression. Cell viability was measured by CCK-8 assay. Transwell assays were performed to evaluate the GC cells' migratory and invasive abilities. Xenograft mouse model was conducted to measure tumor growth.
We found that Linc-ROR were overexpressed in GC tissues compared to the adjacent tissues. High Linc-ROR predicts poor prognosis of GC patients. The prediction of bioinformatics online revealed that Linc-ROR could bind to miR-212-3p. Further, dual-luciferase reporter assay confirmed a direct interaction between Linc-ROR and miR-212-3p. Overexpression of miR-212-3p facilitated GC cells' migration and invasion, while the silencing of miR-212-3p attenuated GC cell migratory and invasive abilities. Moreover, Linc-ROR knockdown significantly suppressed the proliferation, migration, and invasion of GC cells, whereas miR-212-3p antagomir partially reversed Linc-ROR knockdown-induced phenotypes. Fibroblast growth factor 7 (FGF7), a downstream molecule of miR-212-3p, was overexpressed in GC cells. The recovery of FGF7 expression partially reversed the phenotypes caused by Linc-ROR silencing. Mechanistically, silencing of Linc-ROR contributed to the downregulation of CDK4, CDK6, Cyclin D1, N-Cadherin, Vimentin, MMP-9, MMP-2, but caused the upregulation of P21, P27, E-Cadherin, CK-19 in MGC-803 cells; however, FGF7 treatment could reverse the results induced by Linc-ROR silencing. Results in vivo further suggested that Linc-ROR knockdown repressed GC tumor growth, where the expression of miR-212-3p was up-regulated and FGF7 expression was downregulated in tumor tissues of mice.
These findings indicated that Linc-ROR/miR-212-3p/FGF7 axis played an important role in gastric cancer progression. Linc-ROR expression level was associated with the prognosis of GC patients.
Linc-ROR是一种长链非编码RNA，在多种人类癌症中异常表达。我们旨在揭示Linc-ROR在胃癌（GC）进展中的作用。
采用qPCR测定基因表达。通过CCK-8法检测细胞活力。进行Transwell实验以评估GC细胞的迁移和侵袭能力。构建异种移植小鼠模型来测量肿瘤生长。
我们发现与相邻组织相比，Linc-ROR在GC组织中过表达。高Linc-ROR预示着GC患者预后不良。在线生物信息学预测显示Linc-ROR可与miR-212-3p结合。此外，双荧光素酶报告基因实验证实了Linc-ROR与miR-212-3p之间存在直接相互作用。miR-212-3p的过表达促进了GC细胞的迁移和侵袭，而miR-212-3p的沉默减弱了GC细胞的迁移和侵袭能力。此外，Linc-ROR基因敲低显著抑制了GC细胞的增殖、迁移和侵袭，而miR-212-3p拮抗剂部分逆转了Linc-ROR基因敲低诱导的表型。成纤维细胞生长因子7（FGF7）是miR-212-3p的下游分子，在GC细胞中过表达。FGF7表达的恢复部分逆转了Linc-ROR沉默引起的表型。机制上，Linc-ROR的沉默导致MGC-803细胞中CDK4、CDK6、细胞周期蛋白D1、N-钙黏蛋白、波形蛋白、基质金属蛋白酶-9、基质金属蛋白酶-2的下调，但导致P21、P27、E-钙黏蛋白、细胞角蛋白-19的上调；然而，FGF7处理可逆转Linc-ROR沉默诱导的结果。体内实验结果进一步表明，Linc-ROR基因敲低抑制了GC肿瘤生长，在小鼠肿瘤组织中miR-212-3p表达上调，FGF7表达下调。
这些发现表明Linc-ROR/miR-212-3p/FGF7轴在胃癌进展中起重要作用。Linc-ROR表达水平与GC患者的预后相关。
